Neural-immune gut-brain communication in the anorexia of disease

Peripheral administration of toxic bacterial products and cytokines have been used to model the immunological, physiological, and behavioral responses to infection, including the anorexia of disease. The vagus nerve is the major neuroanatomic linkage between gut sites exposed to peripheral endotoxins and cytokines and the central nervous system regions that mediate the control of food intake, and thus has been a major research focus of the neurobiological approach to understanding cytokine-induced anorexia. Molecular biological and neurophysiologic evidence demonstrates that peripheral anorectic doses of cytokines and endotoxins elicit significant increases in neural activation at multiple peripheral and central levels of the gut-brain axis and in some cases may modify the neural processing of meal-related gastrointestinal signals that contribute to the negative feedback control of ingestion. However, behavioral studies of the anorectic effects of peripheral cytokines and endotoxins have shown that neither vagal nor splanchnic visceral afferent fibers supplying the gut are necessary for the reduction of food intake in these models. These data do not rule out 1) the potential contribution of supradiaphragmatic vagal afferents or 2) a modulatory role for immune-stimulated gut vagal afferent signals in the expression of cytokine and enodotoxin-induced anorexia in the intact organism.